Interleukin-10 deficiency increases atherosclerosis, thrombosis, and low-density lipoproteins in apolipoprotein E knockout mice.

Abstract

Interleukin (IL)-10 is an anti-inflammatory cytokine that may play a protective role in atherosclerosis. The aim of this study was to assess the effect of IL-10 deficiency in the apolipoprotein E knockout mouse. Apolipoprotein E deficient (E-/-) and IL-10 deficient (-/-) mice were crossed to generate E-/- x IL-10-/- double knockout mice. By 16 wk, cholesterol and triglycerides were similar in double and single knockouts but the lack of IL-10 led to increased low-density lipoprotein cholesterol whereas very-low-density lipoprotein was reduced. In parallel, T-helper 1 responses and lesion size were dramatically increased in double knockout compared with E-/- controls. At 48 wk, matrix metalloproteinases and tissue factor activities were increased in lesions of double-knockout mice. Furthermore, markers of systemic coagulation were increased, and vascular thrombosis in response to i.v. thrombin occurred more frequently in E-/- x IL-10-/- than in E-/- mice. Our findings suggest that IL-10 deficiency plays a deleterious role in atherosclerosis. The early phase of lesion development was increased, and the proteolytic and procoagulant activity was elevated in advanced lesions. These data show that IL-10 may reduce atherogenesis and improve the stability of plaques.

• Authors: Giuseppina Caligiuri, Mats Rudling, Véronique Ollivier, Marie-Paule Jacob, Jean-Baptiste Michel, Göran K Hansson, Antonino Nicoletti
• Journal: Molecular medicine (Cambridge, Mass.) (Mol Med) 2003 Jan-Feb Vol. 9 Issue 1-2 Pg. 10-7 ISSN: 1076-1551 [Print] England
• PMID: 12765335 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Lipoproteins, LDL
• Lipoproteins, VLDL
• Receptors, LDL
• Interleukin-10
• Matrix Metalloproteinases

Topics

• Animals
• Apolipoproteins E (deficiency, physiology)
• Arteriosclerosis (etiology, genetics, metabolism)
• Blood Coagulation (physiology)
• Crosses, Genetic
• Diet, Atherogenic
• Interleukin-10 (deficiency, physiology)
• Lipoproteins, LDL (metabolism)
• Lipoproteins, VLDL (metabolism)
• Matrix Metalloproteinases (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Phenotype
• Receptors, LDL (metabolism)
• Th1 Cells (immunology)
• Th2 Cells (immunology)
• Thrombosis (etiology, genetics, metabolism)